Thyroid follicles with acid mucins in man: A second kind of follicles?

Summary Human thyroid follicles containing acid mucins have been regarded as a very rare finding and their significance has not yet been clarified. Therefore, a systematic anatomical, histochemical and immunohistochemical survey for the presence of such follicles in human thyroids was undertaken.Follicles with Alcian blue-positive acid mucins were practically confined to the 18% of sections that also contained ultimobranchial solid cell nests. Immunohistochemistry revealed that these follicles were mostly composed of and/or related to the presence of numerous calcitonin-immunoreactive cells, sometimes intermixed with occasional alcianophilic mucinous cells. These findings, with histometrical studies, demonstrate that there exists a relationship between mucinous C cell complexes and mucin/C cell-containing solid cell nests. The finding of calcitonin immunoreactivity in very occasional groups of cells with mucinous changes further suggests that at least some human follicular cells originate in ultimobranchial tissue.     

Morphological and histochemical changes of ultimobranchial follicles of the rat thyroid in the course of postnatal life.

Morphological and histochemical changes of ultimobranchial follicles of thyroid have been investigated in rats from newborn to 18 months of age. The first well-delimited ultimobranchial follicles, though with no lumen, were detected in the thyroid gland of 10-day-old rats. At 30 days of age, follicles possessing regular lumina were present in the thyroid. With age, the follicles gradually increased in volume assuming extreme dimensions in adult age. The follicles displayed varying shapes from simple cysts to bizarre forms. From the age of 50 days the cells of the follicular wall are separated from the cell debris contained in the lumen. The latter gave a PAS positive reaction. The cells of the ultimobranchial follicles did not exhibit argyrophilia and metachromasia showing that they differ considerably from the C-cells likewise of ultimobranchial origin, which are known to give marked argyrophilic and metachromatic reactions.     

Expression of 'visceral' cytokeratin and ultrastructural findings in solid cell nests of the thyroid

Solid cell nests of the thyroid display histological features that resemble squamous epithelium. In the present study we investigated whether these ultimobranchial nests express a renal tubular cell cytokeratin which is found to be widely distributed in epithelia but does not appear in squamous tissue. All 17 solid cell nests studied, in contrast to squamous epithelium lining an intrathyroid thyroglossal cyst, stained positively for this intermediate filament. These findings, together with the gland-like features shown ultrastructurally by these ultimobranchial remnants, further support the view that solid cell nests of the thyroid should not be regarded as a kind of intrathyroid squamous inclusion. In addition, they were electron-microscopically comparable to mammalian ultimobranchial tissue.     

C-cell in vestiges of the ultimobranchial body in human thyroid glands.

Calcitonin-containing cells were demonstrated in the so-called solid cell nests of three human thyroid glands, which supports the theory of the ultimobranchial origin of these cell nests.     

Solid cell nests of the thyroid. An anatomical survey and immunohistochemical study for the presence of thyroglobulin

A systematic anatomical study of 100 adult human thyroids from autopsies was undertaken for the presence of solid cell nests (SCN). SCN were mainly located in the middle third, with a slight tendency to the upper third, of the lateral thyroid lobes, and placed along a central to paracentral and slightly dorsal longitudinal axis. Immunohistochemical studies for thyroglobulin revealed positive staining in follicular cells connected to SCN and, occasionally, in isolated cells lying within solid clusters from SCN. The anatomical position SCN showed in the present survey is comparable to that shown by the ultimobranchial body (UB) vestiges of human fetuses. The presence of thyroglobulin-positive cells within solid clusters, together with the existence of follicular cells connected to SCN, suggest that SCN may also be a probable source of follicular epithelium as occurs with the UB of some mammals.     

Difference between the thyroid gland of normal and hypomyelinated jimpy mice--a light microscopic study

A light microscopic quantitative analysis was performed on normal and jimpy male mice for studying the difference between the structures of the thyroid glands of the two animals. The results of this analysis showed that the thyroid gland of the normal mice consisted of numerous homogenous round follicles with cuboidal follicular cells, separated by thin interlobular and interfollicular connective tissue and a few adipose tissue. The thyroid gland of jimpy mice consisted of a few, small follicles surrounded by columnar follicular cells and intraepithelial capillaries, separated by thick connective tissue and abundant adipose tissue. The number of thyroid follicles are significantly less in the jimpy mice than in the normal mice. Another striking difference is that almost every follicular cell surrounding the follicular lumen of jimpy mice is accompanied by an intraepithelial capillary. In addition, the ratio of the number of intraepithelial capillaries to the number of the thyroid follicular cells are significantly higher in the jimpy mice than in the normal mice. The S-follicles or ultimobranchial cysts of the thyroid gland are well developed in the jimpy mice. The parafollicular cells are normal in appearance. Morphological evidence suggested that the thyroid follicular cells of the jimpy mice are very active in the transport, synthesis and release of thyroglobulin, and secretion of thyroid hormones. But owing to the significantly decreased number of thyroid follicles, the inadequate secretion of the thyroid hormones result in the hypothyroidism and the hypomyelination of the jimpy mice.     

Histological markers of solid cell nests of the thyroid. With some emphasis on their expression in thyroid ultimobranchial-related tumors

It was recently demonstrated that C cells, mucosubstances, and the intermediate filament epidermal keratin are present in solid cell nests (SCN) of the thyroid. The reliability and usefulness of these markers in detecting these ultimobranchial nests have, so far, not been comparatively investigated. In the light of this, a study for the presence of these tracers in SCN at different stages of postnatal life was undertaken. The existence of carcinoembryonic antigen (CEA) in this gut-derived tissue was also searched for. Epidermal keratin was present in the epidermoid-like cells from all SCN studied; calcitonin-immunoreactive C cells and mucosubstances did not always occur. These findings reveal that this cytokeratin would remain as a potential marker to detect and trace back the ultimobranchial tissue component of the thyroid in earlier stages of development. The presence of CEA in practically all SCN surveyed would further support the view that they originate in the gut. This antigen would also be of great value for histological identification of these nests. The usefulness of these markers for the interpretation of the histogenesis of some ultimobranchial-related thyroid neoplastic growths, specifically the medullary and mucoepidermoid carcinomas, is briefly discussed.     

The relation between solid cell nests and C cells of the thyroid gland

Summary Thyroid tissue of 300 routine autopsies was processed in a standardized manner. So-called solid cell nests (SCN) were found in 21 patients (7 %). These cases were investigated carefully by serial step sectioning. In order to explore the correlation of SCN to the C-cell system, the sections were stained by silver impregnation and the immunoperoxidase method. Morphometric analyses revealed a significant increase in the density of C cells in the proximity of the SCN. With progressive distance from the SCN, the C-cell density decreased and reached normal values. In 30 % of the cases argyrophilic and calcitonin-positive cells were found lying within the SCN. Occasionally, mixed follicles could be discerned: These were lined on the one side by a multilayered squamous epithelium, on the other side by normal monolayered cubic follicular epithelium, and contained a peculiar granular material. In one case, SCN were associated with intrathyroid portions of the parathyroids and adult adipose tissue, in a second case with adipose tissue only. Most probably SCN are vestiges of the ultimobranchial body and should be interpreted as such, despite the fact that other authors have expressed different views. The lack of disturbances in the calcium metabolism of the patients and the absence of medullary carcinoma in their family histories led us to interpret locally confined C-cell hyperplasia not as reactive nor premalignant, but rather as normal.     

Development and cytodifferentiation of C cell complexes in dog fetal thyroids

Summary The development of C-cell complexes was investigated in dog fetuses by an immunoperoxidase method with three specific antisera: anti-calcitonin, anti-C-thyroglobulin (C-Tg), and anti-19S thyroglobulin. Ultimobranchial bodies joined with the thyroid anlage and then dispersed into the parenchyma to form large C cell groups. Sparse reaction products of C-Tg initially appeared in C cells with small amounts of cytoplasm. Later at about day 39 of gestation, when the immunoreactivity of calcitonin and 19S thyroglobulin appeared weakly in C cells and follicular cells, C-cell complexes were identified as large cell masses containing numerous undifferentiated cells without no immunoreactivity for any of the antisera. As development proceeded, the undifferentiated cells developed progressively the morphology of C cells. In addition, the undifferentiated cells developed 19S thyroglobulin immunoreactivity, that is, within some of the complexes small clusters of cells filled with material immunoreactive for 19S thyroglobulin. They were not organized into follicles during the fetal period, and were very slow in development. Depending on the degree of development of the undifferentiated cells, several features of the complexes were noted. The present study indicates that not only C cells but also follicular thyroid cells appear to be derived from the ultimobranchial bodies.     

C-cell follicles of canine thyroid glands studied by PAS reaction and electron microscopy

Summary Small follicles composed solely of C cells were occasionally observed in large C cell groups of dog thyroid glands. The lumina of C-cell follicles were filled with, or contained peripheral depositions of PAS-positive amorphous material, which was similar in ultrastructural features to thyroglobulin-containing colloid in typical thyroid follicles. This indicates that C cells, in addition to secreting calcitonin, produce a glycoprotein that can be stored in the lumina of the follicles.     

Ultrastructure of the ultimobranchial follicles of the laying chicken

Summary The ultimobranchial gland of the laying chicken consists of groups of C cells interspersed among a collection of intercommunicating follicles and ducts of variable size and shape. The epithelium lining this system ranges from squamous to columnar and includes stratified squamous and pseudostratified columnar elements. Four cell types are distinguished in this epithelium: F, mucous, C, and basal cells. F cells show microvilli and microfilaments. Pinocytotic activity and images of fusion of coated vesicles with the plasma membrane are evident. The rough-surfaced endoplasmic reticulum (RER) and the Golgi complex are moderately developed. Dense bodies are encountered apically in some cells. Mucous cells possess microvilli and secretory material in the typical form of partially fused droplets. C cells contain secretory granules and are invariably separated from the follicular lumen by other cell types. The smaller, pyramidal basal cells contain filaments, RER, small Golgi complexes, free ribosomes and hemidesmosomes. The lumina contain flocculent or granular material, cellular debris and desquamated cells. Morphological evidence demonstrates that features of the pharyngeal epithelium are retained and that the majority of the cell types, with the exception of C cells, are presumably nonendocrine.Supported by grant HES 75-09030 from the National Science FoundationThe technical assistance of Quan Nguyen is gratefully acknowledged     

Morphological changes in the human thyroid gland cultivated in continual flow system

In the present pilot study, the human thyroid gland tissue was cultivated under continuous culture conditions in the culture chambers of the ACUSYST-S system to determine morphological changes as well as the secretion of thyreoglobulin (Tgl) and thyroid hormones. After 24 hours of cultivation the follicular structure of the tissue was preserved in peripheral parts only, and there were regressive changes in the epithelium center. After 72 hours the regressive changes appeared in isolated follicles only; the size of the follicles increased, the height of the follicular epithelium decreased and there were macrophages present with phagocytized cell debris. After 144 hours disintegration of epithelia took place in the centre, while at the periphery the original follicles survived and very tiny new follicles formed, consisting of only 6 to 8 cells each and surrounding in section the homogeneous colloid. The parenchyma picture suggests a possibility of functional regeneration as an expression of adaptation to the conditions newly arisen during cultivation in a culture chamber. There was no significant influencing of the thyroid hormone secretion during cultivation. On the other hand, the Tgl secretion decreased throughout cultivation.     

Solid cell nests of the thyroid gland. Optic and immunohistochemical study at autopsies.

In order to establish the prevalence of solid cell nests (SCN) in adult thyroids, we studied 100 consecutive glands at necropsy. These were serially sectioned and stained with routine and immunoperoxidase techniques in order to detect calcitonin, carcinoembryonic antigen, thyroglobulin and keratin. SCN may be considered as normal thyroid gland components, and they share with C cells a common origin in the ultimobranchial body.     

Immunohistochemical study of the C-cell complex of dog thyroid glands with reference to the reactions of calcitonin,C-thyroglobulin and 19S thyroglobulin

Summary Continued from the previous study in fetal animals (Kameda et al. 1980), the development and maturation of C-cell complexes in postnatal dogs from newborn to adult were investigated by use of an immunoperoxidase method using antisera to calcitonin, C-thyroglobulin (C-Tg) and 19S thyroglobulin, respectively. The younger the animals were, the more numerous were undifferentiated cells and high columnar epithelial cells in the complexes. With increasing age, the constituent elements of the complexes progressively differentiated. In one type of complex there are a large number of C-cells in various developmental stages, as well as undifferentiated cells and cysts. C-cell complexes composed mostly of mature C-cells were regarded as the more highly differentiated structures of this type. A second type contains follicular cells in various stages of differentiation in addition to undifferentiated cells and C-cells, i.e., 19S-positive cell masses not yet organized into follicles, primordial follicles with small lacunae and comparatively larger follicles. The follicular cells in the complexes were similar with respect to immunoreaction and folliculogenesis to the cells of fetal thyroids, but they developed very slowly. In conclusion, the present study indicates that follicular thyroid cells can differentiate within C-cell complexes, i.e., they develop from cells of ultimobranchial body origin.     

Autoradiographic studies with 3H 1,25 dihydroxyvitamin D3 in thyroid and associated tissues of the neck region

Rats and mice fed a vitamin D-deficient or vitamin D-complete diet were injected with 3H 1,25 (OH)2 vitamin D3. Autoradiograms prepared from cross sections through the neck region revealed nuclear concentration of radioactivity strongest in parathyroid chief cells, occasionally in thyroid follicular epithelial and interfollicular cells, in the epithelium of tubular remnants of the ultimobranchial body, in epithelium of the esophagus, in chondrocytes of tracheal cartilage, and in myoepithelial cells of tracheal glands. In the thyroid, most of the follicle epithelial cells did not show nuclear concentration of radioactivity which occurred only occasionally and predominantly in follicles located in marginal positions. Thyroglobulin in lumina of thyroid follicles contained varying amounts of radioactivity that correspond to the diameter of the follicles, with relatively high amounts in large follicles and little or no radioactivity in small follicles. Competition with excess of unlabeled 1,25 (OH)2 vitamin D3 abolished nuclear radioactivity, but not the radioactivity in the colloid, while 25 (OH) vitamin D3 did not affect either. When a combination of autoradiography and immunohistochemistry was applied, follicular and parafollicular C-cells positive for calcitonin antibodies, did not show nuclear concentration of radioactivity. Tubular remnants of ultimobranchial bodies, however, showed distinct nuclear labeling, but did not stain, or only weakly stain, with antibodies to calcitonin. When 3H 25 (OH) vitamin D3 was injected, no nuclear concentration of radioactivity was noted in any of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunocytochemical studies on differentiation of the thyroid gland in rabbit fetuses and chick embryos

Summary The morphogenesis of the thyroid gland in rabbit fetuses and chick embryos was investigated using the PAS stain and an immunoperoxidase method with anti-19S-thyroglobulin antiserum. In rabbit fetuses, the reaction for precursor components was firstly detected in the apical portions of follicular cells, arranged in clusters but not yet forming follicles, at 16 days of gestation. Although the first primordial follicles storing colloid droplets were observed on day 18, a drastic increase of follicle formation, the true onset of thyroid function, did not occur until day 22. The colloid in primordial follicles revealed very strong immunoreactivity for 19S-thyroglobulin. The follicles gradually increased in size with age. At 25 days of gestation the cytoplasm of follicular cells was stained densely by slightly diluted 19S-thyroglobulin antiserum, whereas the colloid was stained with highly diluted antiserum; these immunoreactions of follicular cells and colloid were comparable to those of postnatal animals. In chick embryos, significant numbers of primordial follicles were observed throughout the whole thyroid parenchyma at 9 days of incubation. On day 12, the follicles stored more PAS-positive and immunoreactive colloid. At 14 days of incubation follicles with enlarged follicular lumina, having an immunoreactivity similar to mature rollicles, became increasingly common.     

New ultrastructural features on the cream hamster thyroid with special reference to the second kind of follicle

The thyroid cells of the cream hamster, characterized by abundance of microtubules and stratification of the organelles, undergo a particular evolution when the animals grow older. These changes are characterized by an increase of the number of lysosomes which in extreme cases become so prominent that they occupy the whole cytoplasm of the cell which thus loses its organelle stratification. As in other species, cream hamster thyroid contains so-called ultimobranchial follicles made up of at least six cell types: fibrillar dark and light cells, parafollicular cells, ciliated cells, vesicular cells, and cells with myelinic inclusions. The ultrastructure of these follicles in the cream hamster represents a mixture of the ultrastructural characteristics of the same follicles encountered in the rat and the mouse thyroid. Here also mixed follicles are seen. Nevertheless vesicular cells present such abundant "secretion granules" that the question arises as to whether these follicles produce a special secretion and perhaps a new hormone. Incubation of cream hamster thyroids in the prescence of vincristine induces vanishing of microtubules, formation of paracrystalline structures, and loss of stratification of the organelles. Although these last effects might be due to some specific toxic effect of the drug, it is suggested that the disappearing of the organelle stratification might result from a specific vincristine-induced disaggregation of the microtubules acting as a cytoskeleton.     

Alterations within the rat thyroid gland during vitamin A deficiency

Thyroid glands from female rats kept vitamin A deficient for one, two, and three months were examined by electron microscopy. After one month on the diet, no consistent alterations were noted. After two months, the colloid in some follicles displayed a peripheral zone of decreased density. In addition, ultimobranchial follicles within the gland had become keratinized. After two to three months on the diet, cells were seen entering the colloid. Many of these cells were identified as follicular cells since they often occurred in groups and occasionally exhibited remnants of desmosomes. Often the cells within the colloid appeared vacuolated, and by light microscopy were thought to contain lipid. However, electron microscopy revealed that these cells contained many digestive vacuoles rather than lipid droplets. Quantitative and autoradiographic studies indicated that thyroids of vitamin A deficient rats took up less radioiodide than thyroids of control rats. The keratinization of ultimorbranchial follicles in vitamin-A deficiency has been suggested as preliminary in the histogenesis of squamous cell carcinoma. However, an effect of vitamin A deficiency on thyroid follicular cells has not heretofore been reported. It's possible that the presence of follicular cells in the colloid reflects an accelerated turnover of these cells and could indicate an early pathological sign.     

Solid cell nests of the human thyroid in early stages of postnatal life. Systematic autopsy study

The anatomical position and prevalence of solid cell nests (SCN) of the thyroid in early stages of postnatal life have not yet been clearly determined. In order to find out about these unsettled questions a systematic search of these ultimobranchial nests from 92 autopsied thyroids from neonates, children and young adults was undertaken. SCN were present in 61% of the patients; they were mainly located in the middle third of the lateral thyroid lobes, and placed along a central to paracentral and slightly dorsal longitudinal axis. These findings, as compared with our previous observations made in older adult thyroids, further demonstrate that there exist a constant anatomical position and prevalence of SCN in postnatal life. The significantly higher frequency of SCN in males (68%) than in females (48%) (p less than 0.01) found in a study that was further extended to 192 thyroids at early and late stages of postnatal life, is a question that requires further investigation.     

Immunohistochemical profiling of the ultimobranchial remnants in the rat postnatal thyroid gland

Ultimobranchial (UB) remnants are a constant presence in the thyroid throughout rat postnatal life; however, the difficulty in identifying the most immature forms from the surrounding thyroid tissue prompted us to search for a specific marker. With that objective, we applied a panel of antibodies reported to be specific for their human counterpart, solid cell nests (SCNs), using double immunohistochemistry and immunofluorescence. Our results demonstrated that cytokeratin 34βE12 and p63 are highly sensitive markers for the immunohistologic screening of UB‐remnants, independently of their maturity or size. Furthermore, rat UB‐follicles (UBFs) coincided with human SCNs in the immunohistochemical pattern exhibited by both antigens. In contrast, the pattern displayed for calcitonin and thyroglobulin differs considerably but confirm the hypothesis that rat UB‐cells can differentiate into both types of thyroid endocrine cells. This hypothesis agrees with recent findings that thyroid C‐cells share an endodermic origin with follicular cells in rodents. We suggest that the persistence of p63‐positive undifferentiated cells in UB‐remnants may constitute a reservoir of basal/stem cells that persist beyond embryogenesis from which, in certain unknown conditions, differentiated thyroid cells or even unusual tumors may arise.